Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice.
Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. Because other chemokines have similar target cell specificities and because CCR2, a cloned MCP-1 receptor, binds other ligands, it has been uncertain whether MCP-1 plays a unique role in recruiting mononuclear cells in vivo. To address this question, we disrupted SCYA2 (the gene encoding MCP-1) and tested MCP-1-deficient mice in models of inflammation. Despite normal numbers of circulating leukocytes and resident macrophages, MCP-1(-/-) mice were specifically unable to recruit monocytes 72 h after intraperitoneal thioglycollate administration. Similarly, accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions was impaired, although the swelling response was normal. Development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs was blunted in MCP-1(-/-) mice, as was expression of IL-4, IL-5, and interferon gamma in splenocytes. In contrast, MCP-1(-/-) mice were indistinguishable from wild-type mice in their ability to clear Mycobacterium tuberculosis. Our data indicate that MCP-1 is uniquely essential for monocyte recruitment in several inflammatory models in vivo and influences expression of cytokines related to T helper responses.
Lu
B
B
Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Rutledge
B J
BJ
Gu
L
L
Fiorillo
J
J
Lukacs
N W
NW
Kunkel
S L
SL
North
R
R
Gerard
C
C
Rollins
B J
BJ
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D018932:Chemokine CCL2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D003877:Dermatitis, Contact / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D015769:Granuloma, Respiratory Tract / Q000276:immunology / Q000469:parasitology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D009163:Mycobacterium bovis / Q000276:immunology; D010641:Phenotype; D012555:Schistosomiasis mansoni / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology
D000947:Antigens, Helminth; D018932:Chemokine CCL2; D016207:Cytokines; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma